The long-term goal of this research is to identify, at the molecular level, those gene products that are causally related to the ability of a cell to produce a tumor in an animal host. Using recombinant DNA technology and a panel of cell lines (with clonal variants) covering the range of tumorigenic potential from normal to highly tumorigenic, the genes uniquely or abundantly expressed in the tumorigenic cell lines will be cloned and characterized. A selected cDNA library from the tumorigenic cell line will be constructed and the genes governing tumorigenicity will be identified, their mRNAs characterized, and their protein products will be characterized and localized within the cell. An alternative approach is to microsequence surface antigens that have been identified only in the more tumorigenic cell lines. Once the sequence is known, oligonucleotide probes can be constructed to isolate the genes' coding for these products. We intend to identify and characterize those products that are involved in enhancing the tumorigenic potential of a transformed cell line, and to initiate studies of the regulation of those genes and the role that they play in the process of tumor formation in the host. (I)